Sickle Cell Disease (SCD) primarily affects the African-American population, in whom the newborn frequency is about 1 in 600. Major clinical manifestations of SCD are caused by the abnormal sickle hemoglobin (HbS), which, when de-oxygenated, polymerizes in the red cell and causes t to become rigid and deformed ("sickled"). This process is thought to be responsible for one of the major clinical manifestations of SCD, recurrent vaso-occlusive painful episodes (VOPEs). Despite the knowledge that sickling can be caused in vitro by de-oxygenation of hemoglobin, the role of common lung diseases which result in hypoxemia, such as reactive airway disease (RAD), in the pathogenesis of VOPEs is unknown. This knowledge is crucial for the following reasons: a) patients with recurrent VOPEs have a shorter life span than those without, b) patients with SCD may have a higher risk of RAD than the normal population, and c) RAD is easily treated with inhaled bronchodilators and anti-inflammatory agents. The specific aims of this study are therefore: 1) to test the hypothesis that children with SCD have a higher prevalence of RAD than a matched population of children without SCD, and to determine the risk factors for, and mechanisms whereby, children with SCD might be more prone to the development of RAD, 2) to test the hypothesis that SCD children with RAD are hypoxemic compared with children without RAD, 3) to test the hypothesis that children with RAD experience more severe and frequent sickle cell pain, and more admitted more frequently for treatment of VOPEs than children without RAD, and that this susceptibility to the development of VOPEs is related to hypoxemia, and 4) to test the hypothesis that treatment of RAD can reduce the frequency and severity of sickle cell pain, and reduce admissions of VOPEs. These aims will be accomplished by measuring lung function. oxygen saturation and bronchial responsiveness in 160 children with SCD and 60 control patients. A longitudinal analysis will then be performed to determine the relationship between lung function (measured by home spirometry and oximetry), and the number and intensity of pain episodes (quantitated by pain diaries) before and during optimal treatment for RAD.